Genetic Variant HMGB1:c.-466_-465delTT (chr13-30464144-TAA-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000399489.5(HMGB1):c.-466_-465delTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 709,112 control chromosomes in the GnomAD database, including 99 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.018 ( 28 hom., cov: 0)

Exomes 𝑓: 0.029 ( 71 hom. )

Consequence

HMGB1
ENST00000399489.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35

Publications

3 publications found

Variant links:

Genes affected

HMGB1 (HGNC:4983): (high mobility group box 1) This gene encodes a protein that belongs to the High Mobility Group-box superfamily. The encoded non-histone, nuclear DNA-binding protein regulates transcription, and is involved in organization of DNA. This protein plays a role in several cellular processes, including inflammation, cell differentiation and tumor cell migration. Multiple pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2015]

HMGB1 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: G2P

HMGB1 links:

ENSG00000285840 (HGNC:):

ENSG00000285840 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000399489.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HMGB1	NM_002128.7	MANE Select	c.-14-452_-14-451delTT	intron	N/A	NP_002119.1	P09429
HMGB1	NM_001313892.2		c.-15+15_-15+16delTT	intron	N/A	NP_001300821.1	P09429
HMGB1	NM_001313893.1		c.-14-452_-14-451delTT	intron	N/A	NP_001300822.1	P09429

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HMGB1	ENST00000399489.5	TSL:1	c.-466_-465delTT	5_prime_UTR	Exon 1 of 5	ENSP00000382412.1	Q5T7C4
HMGB1	ENST00000341423.10	TSL:1 MANE Select	c.-14-452_-14-451delTT	intron	N/A	ENSP00000345347.5	P09429
HMGB1	ENST00000468384.1	TSL:1	n.120-452_120-451delTT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0175

AC:

2615

AN:

149386

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0102

Gnomad ASJ

AF:

0.0230

Gnomad EAS

AF:

0.000392

Gnomad SAS

AF:

0.0267

Gnomad FIN

AF:

0.00298

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0137

Gnomad OTH

AF:

0.0162

GnomAD4 exome

AF:

0.0293

AC:

16423

AN:

559628

Hom.:

AF XY:

0.0298

AC XY:

7729

AN XY:

259690

show subpopulations

African (AFR)

AF:

0.0466

AC:

561

AN:

12038

American (AMR)

AF:

0.0173

AC:

AN:

636

Ashkenazi Jewish (ASJ)

AF:

0.0345

AC:

119

AN:

3450

East Asian (EAS)

AF:

0.00867

AC:

AN:

2422

South Asian (SAS)

AF:

0.0547

AC:

609

AN:

11140

European-Finnish (FIN)

AF:

0.00485

AC:

AN:

206

Middle Eastern (MID)

AF:

0.0403

AC:

AN:

1092

European-Non Finnish (NFE)

AF:

0.0285

AC:

14528

AN:

510224

Other (OTH)

AF:

0.0287

AC:

529

AN:

18420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.416

Heterozygous variant carriers

860

1719

2579

3438

4298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

790

1580

2370

3160

3950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0175

AC:

2618

AN:

149484

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1220

AN XY:

72902

show subpopulations

African (AFR)

AF:

0.0309

AC:

1266

AN:

40962

American (AMR)

AF:

0.0101

AC:

152

AN:

14998

Ashkenazi Jewish (ASJ)

AF:

0.0230

AC:

AN:

3432

East Asian (EAS)

AF:

0.000393

AC:

AN:

5084

South Asian (SAS)

AF:

0.0263

AC:

125

AN:

4746

European-Finnish (FIN)

AF:

0.00298

AC:

AN:

9726

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0137

AC:

920

AN:

67272

Other (OTH)

AF:

0.0160

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

132

263

395

526

658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0103

Hom.:

2131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Mutation Taster

=299/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

13-30464144-TAAAAA-TAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over